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| Name | Class |
|---|---|
| Hainan General Hospital | OTHER |
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This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or combined with chemotherapy or combined with chemotherapy and checkpoint inhibitor in the treatment of pediatric high-risk and refractory/relapsed neuroblastoma in Sun Yat-sen University Cancer Center.
Patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation received axitamab and GM-CSF. Patients with high-risk neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory) received naxitamab and GM-CSF in combination with irinotecan and temozolomide or naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| naxitamab and GM-CSF only | Other | Suitable for patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation. The treatment cycle is repeated every 4 weeks for a total of 5 courses, and discontinuation of nasetuzumab and GM-CSF should be considered if disease progression or unacceptable toxicity occurs. |
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| naxitamab and GM-CSF in combination with irinotecan and temozolomide | Other | Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures. |
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| naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody | Other | Suitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naxitamab monotherapy | Drug | Naxitamab is administered on days 1, 3, and 5 |
|
| Measure | Description | Time Frame |
|---|---|---|
| ORR | The proportion of patients who achieved CR or PR | from start of naxitamab treatment to 1.5 years after EOT |
| Measure | Description | Time Frame |
|---|---|---|
| DCR | The proportion of patients who achieved CR or PR or SD | from start of naxitamab treatment to 1.5 years after EOT |
| EFS | The time from from start of naxitamab treatment to disease progression, recurrence |
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Inclusion Criteria:
1)Confirmed diagnosis of high-risk NB 2)1 year of age or above 3)Patient or parent/guardian must provide written informed consent to participate 4)If patient is sexually active, the patient agrees to use effective contraception 5)Confirmed negative urine pregnancy test for sexually active female of child-bearing potential (post-menarche)
Exclusion Criteria:
Significant organ toxicity
Known or suspected allergy or hypersensitivity to anti-GD2 antibodies or to GM-CSF or its s components.
Patient is pregnant, planning to become pregnant (while being treated with naxitamab) or is currently breastfeeding
Patient will undergo treatment with another investigational drug, whilst being treated with naxitamab or has received another investigational drug within the 4 weeks prior to commencing treatment with naxitamab
Patient is either eligible and able to participate in or is currently participating in an active interventional Y-mAbs sponsored clinical trial with naxitamab within the indication applied for
Patient is unable to comply with the naxitamab treatment or has a medical condition that would potentially increase the severity of the toxicities experienced from naxitamab treatment at the discretion of the treating physician
Left ventricular ejection fraction of <50% by echocardiography OR other clinically relevant cardiac disorders at the discretion of the investigator
Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated
Applicable for treatment with naxitamab in combination with GM-CSF only:
Patient has active progression of the NB disease
Patient has active NB disease at primary site or soft-tissue metastasis
Patient has known CNS metastases when initiating naxitamab treatment
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yizhuo Zhang, MD | Contact | 0087342460 | zhangyzh@sysucc.org.cn | |
| Juan Wang | Contact | 008687342660 | wangjuan@sysucc.org.cn |
| Name | Affiliation | Role |
|---|---|---|
| Yizhuo Zhang | SunYat Sen University Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
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| GM-CSF | Drug | Each treatment cycle is 28 days and is started with five days (days -4 to 0) of GM-CSF administered at 250 mcg/m2/day in advance of the start of naxitamab infusion. GM-CSF is thereafter administered at 500 mcg/m2/day on days 1 to 5. |
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| Irinotecan | Drug | Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day. |
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| Temozolomide | Drug | Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day. |
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| Naxitamab in combination therapy | Drug | Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10. |
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| GM-CSF with combination regimen | Drug | GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10. |
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| Sintilimab | Drug | Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks. |
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| from start of naxitamab treatment to 1.5 years after EOT |
| OS | The time from from start of naxitamab treatment to death or loss of follow-up | from start of naxitamab treatment to 1.5 years after EOT |
| ID | Term |
|---|---|
| D009447 | Neuroblastoma |
| ID | Term |
|---|---|
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| C000718263 | naxitamab |
| D016178 | Granulocyte-Macrophage Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D000077146 | Irinotecan |
| D059004 | Topoisomerase I Inhibitors |
| D000077204 | Temozolomide |
| D007267 | Injections |
| D003131 | Combined Modality Therapy |
| C000632826 | sintilimab |
| C000711728 | spartalizumab |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D059003 | Topoisomerase Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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